Sulfoxonium, trimethyl-, iodide (1:1) → Tert-butyl 2-(4-bromophenyl)cyclopropanecarboxylate

HRID 533687노트

반응식

HRID 533687 반응식
[I-].C[S+](C)(C)=O.[CH3:7]C(C)([O-])C.[Na+].[Br:13][C:14]1[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][CH:15]=1.[S]>CS(C)=O.CC(N(C)C)=O>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([CH:20]2[CH2:7][CH:21]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:18][CH:19]=1

참가 물질

7

반응물 4

HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 5362487SulfurHCID 11482956tert-Butyl (2E)-3-(4-bromophenyl)prop-2-enoateHCID 23676156Sodium t-butoxide

생성물 1

HCID 16744563Tert-butyl 2-(4-bromophenyl)cyclopropanecarboxylate수율 74.7%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매2회HCID 31374Dimethylacetamide용매

실험 절차

In a round-bottom flask, mixed trimethylsulfoxonium iodide (6.6 g, 30 mmol) in dimethyl sulfoxide (28 mL, KF=266 ppm H2O) and dimethylacetamide (12 mL, KF=249 ppm H2O). Added sodium tert-butoxide (2.7 g, 28 mmol) in one portion. Stirred the suspension for NLT 0.5 H at room temperature. Separately, mixed (E)-tert-butyl 3-(4-bromophenyl)acrylate 1 (5.66 g, 20 mmol) in dimethyl sulfoxide (20 mL) and heated to 50° C. Then, transferred the sulfur ylide mixture (slight suspension) by cannula (<10 min addition). The flask/cannula were rinsed into the reaction mixture with dimethyl sulfoxide (2-4 mL). Stirred the resulting yellow solution at 50° C., monitoring by HPLC for reaction completion (<1% pA of 1 after 0.5 h). Cooled the reaction mixture to <10° C. before quenching (exothermic) by slow addition with water (120 mL, product precipitates). The resulting product slurry was stirred at room temperature (1-2 h) and then filtered. The flask and wetcake were washed with water (˜70 mL total). The wetcake was dried under vacuum at 45° C. Isolated 4.44 g of an off-white solid (98% pA, 96 wt %) in 71% wt-adjusted yield. A sample of the isolated product was further purified by crystallization from methanol/water (1:1, 20 mL/g). 1H NMR (400 MHz, CDCl3) δ 1.16-1.21 (m, 1H), 1.47 (s, 9H), 1.50-1.55 (m, 1H), 1.77-1.81 (m, 1H), 2.37-2.41 (m, 1H), 6.95 (d, 2H, J=8.37), 7.37 (d, 2H, J=8.51). 13C NMR (100 MHz, CDCl3) δ 17.3, 25.4, 25.5, 28.4, 80.7, 119.7, 127.5, 131.1, 139.2, 171.7 with 4 peaks overlapping.

후처리

  1. temperatureheated to 50° C
  2. additionby cannula (<10 min addition)
  3. washThe flask/cannula were rinsed into the reaction mixture with dimethyl sulfoxide (2-4 mL)
  4. stirringStirred the resulting yellow solution at 50° C.
  5. custommonitoring by HPLC for reaction completion (<1% pA of 1 after 0.5 h)
  6. temperatureCooled the reaction mixture to <10° C.
  7. custombefore quenching (exothermic)
  8. additionby slow addition with water (120 mL, product precipitates)
  9. stirringThe resulting product slurry was stirred at room temperature (1-2 h)
  10. filtrationfiltered
  11. washThe flask and wetcake were washed with water (˜70 mL total)
  12. customThe wetcake was dried under vacuum at 45° C

출처 및 근거

ORD 기록
ord-9b1fc298476c493395362d21930bf103
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853390B2

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